CT-P10 Shows Comparable Efficacy to Rituxan in Network Meta-Analysis

The rituximab biosimilar CT-P10 (Celltrion and Teva’s Truxima), which is approved in the European Union and under review by the FDA in the United States, showed comparable effectiveness to reference rituximab (Genentech and Biogen’s innovator product, sold as Mabthera and Rituxan) in a network meta-analysis conducted by Marco Chiumente, PharmD, and colleagues, which was published in the September 2017 issue of Haematologica. Network meta-analysis is increasingly used because of its ability to compare 3 or more treatments with one another—a feature particularly helpful for studying biosimilars, the authors note.

A recent European Public Assessment Report by the European Medicines Agency (EMA) that assessed CT-P10 was used as the basis for the authors’ network meta-analysis, which included an equivalence study comparing CT-P10 versus the originator rituximab in patients with advanced follicular lymphoma (AFL) as well as a randomized clinical trial comparing the originator rituximab versus the standard of care (SOC). The SOC included chemotherapy regimens that are commonly recommended in AFL, such as cyclophosphamide, vincristine, and prednisone (CVP).

There were 1704 evaluable patients in the meta-analysis. The study’s endpoint was the rate of overall response at the end of the prescribed regimens, a composite of complete response, unconfirmed complete response, and partial response. The network meta-analysis was based on the Bayesian method proposed by the National Institute for Health and Care Excellence (NICE) and estimated odds ratio (OR) for all pairwise comparisons, along with ranking histogram and 95% credible intervals (CrI).

The authors found an OR of:

• 2.61 (95% CrI, 0.51 to 14.91) for the comparison biosimilar versus originator
• 7.44 (95% CrI, 1.42 to 43.38) for the biosimilar versus stanzas of care (SOC)
• 2.82 (95% CrI, 2.14 to 3.76) for originator rituximab versus SOC

In terms of efficacy, CT-P10 ranked as follows:

• First in 88% of Bayesian simulations
• Second in 12%
• Third in 0%

Originator rituximab ranked as follows:

• First in 12%
• Second in 88%
• Third in 0%

The SOC always ranked third.

The 95% CrI estimated by the Bayesian meta-analysis for the comparison of biosimilar versus originator (OR = 2.61; 95% CrI, 0.51 to 14.91) was close to the 95% confidence interval (CI) reported in the equivalence trial (OR = 2.56; 95% CI, 0.48 to 14.28). “Hence, the results of our network meta-analysis concerning this comparison (together with their variability) confirmed those found in the equivalence trial,” the authors conclude. “The results of our meta-analysis confirm the efficacy of rituximab biosimilar in treating AFL.” They further point out that the biosimilar ranked first in 88% of the Bayesian simulations.

“Using CT-P10 in patients with AFL has a critical clinical relevance because, at least in Europe, this is the first case in which a biosimilar has been proposed for a potentially curative indication in oncologic patients,” the researchers conclude. Globally, national healthcare systems are spending approximately $100 billion per year for anticancer drugs alone. Researchers continue to study biosimilars’ efficacy and safety compared with originator drugs because using biosimilars can reduce the costs of cancer treatments and increase accessibility to these important treatments. The authors conclude that, if physicians are to consider using biosimilars, it is important to confirm their comparability in terms of pharmacokinetics and pharmacodynamics, preclinical biological activity, and physiochemical characterization, and also critical to require a robust and consistent manufacturing process.